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Background: This study aimed to clarify the efficacy and safety of minimally invasive transabdominal surgery (MIS) with transperineal minimal invasive surgery (tpMIS) for sacrectomy in advanced primary and recurrent pelvic malignancies. Methods: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of MIS with tpMIS for sacrectomies. Surgery was performed between February 2019 and May 2023. The median follow-up period was 27 months (5–46 months). Results: Fifteen consecutive patients were included in this analysis. The diagnoses were as follows: recurrent rectal cancer, n = 11 (73%); primary rectal cancer, n = 3 (20%); and recurrent ovarian cancer, n = 1 (7%). Seven patients (47%) underwent pelvic exenteration with sacrectomy, six patients (40%) underwent abdominoperineal resection (APR) with sacrectomy, and two patients (13%) underwent tumor resection with sacrectomy. The median intraoperative blood loss was 235 ml (range 45–1320 ml). The postoperative complications (Clavien–Dindo grade ≥ 3a) were graded as follows: 3a, n = 6 (40%); 3b, n = 1 (7%); and ≥ 4, n = 0 (0%). Pathological examinations demonstrated that R0 was achieved in 13 patients (87%). During the follow-up period, two patients (13%) developed local re-recurrence due to recurrent cancer. The remaining 13 patients (87%) had no local disease. Fourteen patients (93%) survived. Conclusions: Although the patient cohort in this study is heterogeneous, MIS with tpMIS was associated with a very small amount of blood loss, a low incidence of severe postoperative complications, and an acceptable R0 resection rate. Further studies are needed to clarify the long-term oncological feasibility. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to clarify the efficacy and safety of transanal minimally invasive surgery (TAMIS) for total pelvic exenteration (TPE) in advanced primary and recurrent pelvic malignancies. Methods: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of TAMIS for TPE. Surgery was performed between September 2019 and April 2023. The median follow-up period was 22 months (2–45 months). Results: Fifteen consecutive patients were included in this analysis M:F = 14:1 and median (range) age was 63 (36–74). Their diagnoses were as follows: primary rectal cancer (n = 5; 33%), recurrent rectal cancer (n = 4; 27%), primary anorectal cancer (n = 5; 33%), and gastrointestinal stromal tumor (n = 1; 7%). Bladder-sparing TPE was selected for two patients (13%). In nine of 15 patients (60%) the anal sphincter could be successfully preserved, five patients (33%) required combined resection of the internal iliac vessels, and two (13%) required rectus muscle flap reconstruction. The median operative time was 723 min (561–1082), and the median intraoperative blood loss was 195 ml (30–1520). The Clavien–Dindo classifications of the postoperative complications were as follows: grade 0–2 (n = 11; 73%); 3a (n = 3; 20%); 3b (n = 1; 7%); and ≥ 4 (n = 0; 0%). No cases of conversion to laparotomy or mortality were observed. The pathological results demonstrated that R0 was achieved in 14 patients (93%). Conclusions: The short-term outcomes of this initial experience proved that this novel approach is feasible for TPE, with low blood loss, acceptable postoperative complications, and a satisfactory R0 resection rate. [ABSTRACT FROM AUTHOR]

Background: Histamine participates in the immune regulation of several gastrointestinal diseases. However, the effect of histamine on intestinal intraepithelial lymphocytes (IELs), the front line of the intestinal mucosal immune system, is not well understood. We examined whether histamine has a direct effect on cytokine production by IELs and the involvement of histamine receptor subtypes.Methods: Murine IELs were activated by PMA plus ionomycin with/without histamine. Secreted cytokines were measured and compared with those of splenocytes. Intracellular cytokines were detected by flow cytometry. Expression of histamine receptor subtypes in IELs was examined by RT-PCR.Results: Histamine H(1) receptor (H(1)R), H(2)R, and H(4)R, but not H(3)R mRNA were expressed on IELs. Histamine significantly decreased Th1-cytokine (IFN-gamma, TNF-alpha, and IL-2) and also IL-4 production in IELs as well as splenocytes. The selective H(2)R antagonist famotidine, but not the H(1)R antagonist pyrilamine nor the H(3)R/H(4)R antagonist thioperamide, competes with the inhibitory effect of histamine on these cytokine production in IELs. These suppressive effects of histamine were mimicked by a selective H(2)R/H(4)R agonist dimaprit. Further, these suppressive effects of histamine for Th1-cytokine and IL-4 did not accompany the enhancement of IL-10 production or IL-10 mRNA level in IELs. Intracellular cytokine analysis revealed that the number of IFN-gamma-producing alphabeta T cells was significantly reduced by histamine in IELs.Conclusions: Histamine has a direct suppressive effect on IEL-derived cytokines via H(2)R, which would have a crucial role in the suppression of local immunoregulation in the intestinal epithelium. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma (MM) is one of the most aggressive neoplasms usually associated with asbestos exposure and is highly refractory to current therapeutic modalities. MMs show frequent activation of a transcriptional coactivator Yes-associated protein (YAP), which is attributed to the neurofibromatosis type 2 (NF2)-Hippo pathway dysfunction, leading to deregulated cell proliferation and acquisition of a malignant phenotype. However, the whole mechanism of disordered YAP activation in MMs has not yet been well clarified. In the present study, we investigated various components of the NF2-Hippo pathway, and eventually found that MM cells frequently showed downregulation of LIM-domain protein AJUBA, a binding partner of large tumor suppressor type 2 (LATS2), which is one of the last-step kinases of the NF2-Hippo pathway. Although loss of AJUBA expression was independent of the alteration status of other Hippo pathway components, MM cell lines with AJUBA inactivation showed a more dephosphorylated (activated) level of YAP. Immunohistochemical analysis showed frequent downregulation of AJUBA in primary MMs, which was associated with YAP constitutive activation. We found that AJUBA transduction into MM cells significantly suppressed promoter activities of YAP-target genes, and the suppression of YAP activity by AJUBA was remarkably canceled by knockdown of LATS2. In connection with these results, transduction of AJUBA-expressing lentivirus significantly inhibited the proliferation and anchorage-independent growth of the MM cells that harbored ordinary LATS family expression. Taken together, our findings indicate that AJUBA negatively regulates YAP activity through the LATS family, and inactivation of AJUBA is a novel key mechanism in MM cell proliferation. [ABSTRACT FROM AUTHOR]

Zebrafish kidney marrow (ZKM), which is equivalent to tire haematopoietic bone marrow of mammals, produces all major blood cell types, which morphologically resemble their mammalian counterparts. To be able to exploit the advantages of zebrafish genetics for analysis of the general mechanisms controlling self-renewal, proliferation and lineage decisions of vertebrate haematopoetic cell populations, it is essential to develop a simple surgical technique in order to identify, dissect and take out the ZKM without contamination with other surrounding tissues and cells. However, the size of adult zebrafish is small (average size: 2.5 cm) and the ZKM is an extremely protected organ and not easy to localize, which makes this procedure a great microsurgical challenge. Here we report a new microsurgical technique to identify, localize and dissect ZKM in adult zebrafish using a new approach. The potential advantages of this technique are summarized here: it allows purity of the sample, which is critical for performing flow cytometry analysis and/or cell number count; it enables visualization of the ZKM without a parenchimal incision, which simplifes the further dissection; the learning curve is short, requiring only basic microsurgical skills, and it is reliable and highly reproducible. To further characterize the kidney marrow cells obtainned by this technique, we performed histology, flow cytometry, cytospin experiments and cell counts. [ABSTRACT FROM AUTHOR]